title: Nanosuspension for improving the bioavailability of a poorly soluble drug and screening of stabilizing agents to inhibit crystal growth.
abstract: The purpose of this study was to develop a nanosuspension of a poorly soluble drug by nanomilling process using wet media milling to achieve superior in vitro dissolution and high in vivo exposure in pharmacokinetic studies. A promising nanosuspension was developed with Vitamin E TPGS based formulation with particle size in the nano range. Although the formulation showed significant improvement during in vitro dissolution and in vivo plasma level, probably due to the strong hydrophobic interaction between Vitamin TPGS and the drug molecule, crystal growth was observed during stability studies. A systematic study was done with different combinations of solubilizer/stabilizer system in order to obtain a more stable nanosuspension. Hydroxypropyl methylcellulose (HPMC 3 cps) was found to stabilize the nanosuspension by better surface coverage due to stronger interaction with the drug as compared to other stabilizers used in this study.
authors.affiliation: Pharmaceutical and Analytical Development, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA. indrajit.ghosh@novartis.com
authors.forename: Indrajit
authors.initials: I
authors.lastname: Ghosh
authors.forename: Sonali
authors.initials: S
authors.lastname: Bose
authors.forename: Radha
authors.initials: R
authors.lastname: Vippagunta
authors.forename: Ferris
authors.initials: F
authors.lastname: Harmon
mesh_terms: D000818:Animals; D001570:Benzodiazepinones / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D003460:Crystallization; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D065347:Hypromellose Derivatives; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D053758:Nanoparticles; D010316:Particle Size; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D013535:Suspensions; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D001570:Benzodiazepinones; D004337:Drug Carriers; D005079:Excipients; D010671:Phenylurea Compounds; D013535:Suspensions; D014810:Vitamin E; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D008747:Methylcellulose; C014225:tocophersolan